Controlled Trial of High-risk Coronary Intervention With Percutaneous Left Ventricular Unloading (CHIP-BCIS3)

Over 100,000 coronary stent procedures, where small balloons are used to stretch open a narrowed blood vessel, are performed every year in the United Kingdom to treat people who have conditions such as angina or have suffered a heart attack.

For most patients the risk of complications is low, but for some, there is a higher risk of their heart failing during the procedure. Heart failure is a serious complication which can need treatment with a life support machine and lead to major damage to the heart muscle or even death. These risks are greatest in patients with severely diseased heart arteries and those who already have weakened heart muscle.

A new technology may be able to help with this problem. It consists of a small heart pump which is placed in the heart's main pumping chamber (the left ventricle, LV). This pump is known as a LV unloading device. The LV unloading device is inserted into the heart through a blood vessel in the leg and supports the heart muscle. It is removed at the end of the procedure or when the heart can pump safely on its own. Whilst this heart pump is promising, it comes with some risks of its own. These include bleeding and damage to the arteries in the legs. It is also expensive, costing £8,000 per operation. Currently, there is no strong evidence to guide the use of this device.

The CHIP-BCIS3 study aims to determine whether these heart pumps are beneficial and cost-effective in patients receiving a stenting procedure who are at high-risk of complications.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Ischemic Heart Disease
• Intervention / Treatment: Device: Percutaneous left ventricular unloading

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Matt Ryan; Email: matthew.ryan@kcl.ac.uk
• Study Contact Backup: Name: Trial Manager; Phone Number: 020 7927 2723; Email: CHIP-BCIS3@LSHTM.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • Guy's and St Thomas' NHS Foundation Trust
    • Contact: R&D Office; Email: R&D@gstt.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Extensive coronary disease defined by a British Cardiovascular Intervention Society (BCIS) Jeopardy Score ≥ 8*
2. Severe left ventricular systolic dysfunction defined as a LVEF ≤ 35% (or ≤ 45% in the presence of severe mitral regurgitation)#

3. Complex PCI defined by the presence of at least one of the following criteria:

   • Unprotected left main intervention in the presence of

     • an occluded dominant right coronary artery, or
     • a left dominant circulation, or
     • disease involving the entire bifurcation (Medina1,1,1 or 0,1,1)

   • Intended calcium modification (by rotational atherectomy, lithotripsy or laser) o inmultiplevesselsor

     • in the left main stem, or
     • in a final patent conduit, or
     • where the anatomic SYNTAX score is ≥32

   • Target vessel is a chronic total occlusion with planned retrograde approach * In general, patients who do not have bypass grafts will be eligible if the patient has at least proximal left anterior descending (LAD) disease or at least proximal 2 vessel disease. For patients with patent bypass grafts, or in cases where the extent of coronary artery disease (CAD) is uncertain, the BCIS-1 JS should be calculated. The maximum possible JS score is 12. N.B. The JS should be based on all coronary disease, not just the vessel subtending viable myocardium.

     • Biplane / 3D echocardiography, or cardiac MRI can be used to assess the qualifying LVEF.

Exclusion Criteria:

1. Cardiogenic shock or acute STEMI at randomisation (including current treatment with a mechanical circulatory support device)
2. Contraindication to pLVAD insertion
3. Inability to give informed consent
4. Previously enrolled in CHIP or current enrolment in another interventional study that may affect CHIP outcomes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LV-unloading; Participants in the elective unloading (intervention) group will have a percutaneous left ventricular unloading device (pLVAD) inserted at the start of the procedure, before the coronary intervention. Maximal support will be provided throughout the procedure, following which support will be weaned and the device removed should the patient remain haemodynamically stable.	Device: Percutaneous left ventricular unloading; Percutaneous left ventricular unloading involves the placement of a mechanical pump which draws blood from the left ventricle and returns it into the aorta at flow rates approaching native cardiac output.
No Intervention: Standard of Care; Participants in the control arm will receive the planned high-risk percutaneous coronary intervention as is the current standard of care without elective left ventricular unloading. Alternative mechanical circulatory support devices (such as the intra-aortic balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO) will only be permitted in case of complications.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite hierarchical outcome analysed using a Win Ratio method.	Events included in the composite hierarchical outcome include: death, stroke, spontaneous myocardial infarction, cardiovascular hospitalisation or periprocedural myocardial infarction.	Minimum 12-months of follow-up, up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual components of the primary outcome including: death, stroke, spontaneous myocardial infarction, cardiovascular hospitalisation or periprocedural myocardial infarction.	Analysis will include repeated occurrences of these events	Minimum 12-months of follow-up, up to 4 years
Completeness of revascularisation measured by the change in anatomic BCIS-JS score		Between baseline and the completion of the final planned PCI procedure assessed up to 90 days post-randomisation
Completeness of revascularisation measured by the change in anatomic SYNTAX score		Between baseline and the completion of the final planned PCI procedure assessed up to 90 days post-randomisation
Major bleeding (BARC 3 or 5) using the Bleeding Academic Research Consortium (BARC) classification		Up to 90 days post-randomisation
Vascular complication measured as the incidence of injury to a major artery or vein resulting in either major bleeding, tissue ischaemia/necrosis requiring percutaneous or surgical intervention, or death		At discharge from each planned percutaneous coronary intervention procedure up to 90 days post-randomisation
Procedural complication measured as the incidence of VT/VF requiring defibrillation, cardiorespiratory arrest, acute pulmonary oedema requiring assisted ventilation or prolonged hypotension		At discharge from each planned percutaneous coronary intervention procedure up to 90 days post-randomisation
Unplanned revascularisation		Up to 90 days post-randomisation
Health-related quality of life and functional status measured by the EuroQol 5-Dimension 5-level questionnaire (EQ-5D- 5L)	The EuroQol 5-Dimension 5-level questionnaire (EQ-5D- 5L) measures quality of life and functional status with higher scores indicating better outcomes.	90 days and 1 year post-randomisation
Resource utilisation and cost effectiveness measured by incremental costs		At 12-months post-randomisation
Resource utilisation and cost effectiveness measured by quality-adjusted life years (QALYs)		At 12-months post-randomisation
Resource utilisation and cost effectiveness measured by net monetary benefit		At 12-months post-randomisation

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: London School of Hygiene and Tropical Medicine; King's College London; St Thomas' Hospital, London; Royal Sussex County Hospital; The Queen Elizabeth Hospital; St. George's Hospital, London; The Royal Bournemouth Hospital; Leeds General Infirmary; New Cross Hospital, Wolverhampton; King's College Hospital, London; Royal Victoria Hospital, Belfast; Bristol Heart Institute; Freeman Hospital, Newcastle; Barts Heart Centre, London; Glenfield Hospital, Leicester; Morriston Hospital, Swansea
• Investigators: Principal Investigator: Divaka Perera, KCL, GSTT

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2021
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: July 21, 2021
• First Submitted That Met QC Criteria: August 6, 2021
• First Posted (Actual): August 12, 2021

Study Record Updates

• Last Update Posted (Estimated): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; percutaneous left ventricular unloading
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia
• Other Study ID Numbers: IRAS290599; 130593 (Other Grant/Funding Number: NIHR HTA CET); 17730734 (Registry Identifier: ISRCTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No